title: Simultaneously enantiospecific determination of (+)-trans-khellactone, (+/-)-praeruptorin A, (+/-)-praeruptorin B, (+)-praeruptorin E, and their metabolites, (+/-)-cis-khellactone, in rat plasma using online solid phase extraction-chiral LC-MS/MS.
abstract: Many chiral drugs are used as the racemic mixtures in clinical practice. The occurrence of enantioselectively pharmacological activities calls for the development of enantiospecific analytical approaches during pharmacokinetic studies of enantiomers. Sample preparation plays a key role during quantitative analysis of biological samples. In current study, a rapid and reliable online solid phase extraction-chiral high performance liquid chromatography-tandem mass spectrometry (online SPE-chiral LC-MS/MS) method was developed for the simultaneously enantiospecific quantitation of (+)-trans-khellactone (dTK), (+/-)-cis-khellactone (d/lCK), (+/-)-praeruptorin A (d/lPA), (+/-)-praeruptorin B (d/lPB) and (+)-praeruptorin E (dPE), the main active angular-type pyranocoumarins (APs) in Peucedani Radix (Chinese name: Qian-hu) or the major metabolites of those APs, in rat plasma. The validation assay results described here show good selectivity and enantiospecificity, extraction efficiency, accuracy and precision with quantification limits (LOQs) of 2.57, 1.28, 1.28, 1.88, 4.16, 4.16 and 4.18ngmL(-1) for dTK, lCK, dCK, dPA, dPB, lPB and dPE, respectively, while lPA was not detected in rat plasma due to the carboxylesterase(s)-mediated hydrolysis. In addition, the validated system was satisfactorily applied to characterize the pharmacokinetic properties of those components in normal and chronic obstructive pulmonary disease (COPD) rats following oral administration of Qian-hu extract. dCK and lCK were observed as the main herb-related compounds in plasma. Enantioselectively pharmacokinetic profiles occurred for dCK vs lCK, dPA vs lPA, and dPB vs lPB in either normal or COPD rats. The proposed whole system is expected to be a preferable analytical tool for in vivo study of chiral drugs, in particular for the characterization of enantioselectively pharmacokinetic profiles.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macao.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Song
authors.forename: Wanghui
authors.initials: W
authors.lastname: Jing
authors.forename: Fengqing
authors.initials: F
authors.lastname: Yang
authors.forename: Zhan
authors.initials: Z
authors.lastname: Shi
authors.forename: Meicun
authors.initials: M
authors.lastname: Yao
authors.forename: Ru
authors.initials: R
authors.lastname: Yan
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000737:chemistry* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D006868:Hydrolysis; D016014:Linear Models; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D003374:Coumarins; C441070:praeruptorin A; C036455:praeruptorin E; C065837:anomalin; C520900:khellactone
keywords: Chiral LC–MS/MS; Enantiospecific; Online SPE; Peucedani Radix; Pharmacokinetics